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1. Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases

Author

Bootsma, Sanne, Dings, Mark P.G., Kesselaar, Job, Helderman, Roxan F.C.P.A., van Megesen, Kyah, Constantinides, Alexander, Moreno, Leandro Ferreira, Stelloo, Ellen, Scutigliani, Enzo M., Bokan, Bella, Torang, Arezo, van Hooff, Sander R., Zwijnenburg, Danny A., Wouters, Valérie M., van de Vlasakker, Vincent C.J., Galanos, Laskarina J.K., Nijman, Lisanne E., Logiantara, Adrian, Veenstra, Veronique L., Schlingemann, Sophie, van Piggelen, Sterre, van der Wel, Nicole, Krawczyk, Przemek M., Platteeuw, Johannes J., Tuynman, Jurriaan B., de Hingh, Ignace H., Klomp, Jan P.G., Oubrie, Arthur, Snaebjornsson, Petur, Medema, Jan Paul, Oei, Arlene L., Kranenburg, Onno, Elbers, Clara C., Lenos, Kristiaan J., Vermeulen, Louis, and Bijlsma, Maarten F.

Published
2024
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5. Molecular characterization of colorectal cancer related peritoneal metastatic disease

Author

Lenos, Kristiaan J., Bach, Sander, Ferreira Moreno, Leandro, ten Hoorn, Sanne, Sluiter, Nina R., Bootsma, Sanne, Vieira Braga, Felipe A., Nijman, Lisanne E., van den Bosch, Tom, Miedema, Daniel M., van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P., Stransky, Nicolas, Smolen, Gromoslaw A., Coebergh van den Braak, Robert R. J., IJzermans, Jan N. M., Martens, John W. M., Hallam, Sally, Beggs, Andrew D., Kops, Geert J. P. L., Lansu, Nico, Bastiaenen, Vivian P., Klaver, Charlotte E. L., Lecca, Maria C., El Makrini, Khalid, Elbers, Clara C., Dings, Mark P. G., van Noesel, Carel J. M., Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J. A., Tanis, Pieter J., de Hingh, Ignace H., Bijlsma, Maarten F., Tuynman, Jurriaan B., and Vermeulen, Louis

Published
2022
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6. A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues

Author

de Back, Tim R, primary, Wu, Tan, additional, Schafrat, Pascale JM, additional, ten Hoorn, Sanne, additional, Tan, Miaomiao, additional, He, Lingli, additional, van Hooff, Sander R, additional, Koster, Jan, additional, Nijman, Lisanne E, additional, Vink, Geraldine R, additional, Beumer, Inès J, additional, Elbers, Clara C, additional, Lenos, Kristiaan J, additional, Sommeijer, Dirkje W, additional, Wang, Xin, additional, and Vermeulen, Louis, additional

Published
2024
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7. A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues

Author

Onderzoek Medische Oncologie, Cancer, de Back, Tim R., Wu, Tan, Schafrat, Pascale J.M., Hoorn, Sanne Ten, Tan, Miaomiao, He, Lingli, van Hooff, Sander R., Koster, Jan, Nijman, Lisanne E., Vink, Geraldine R., Beumer, Inès J., Elbers, Clara C., Lenos, Kristiaan J., Sommeijer, Dirkje W., Wang, Xin, Vermeulen, Louis, Onderzoek Medische Oncologie, Cancer, de Back, Tim R., Wu, Tan, Schafrat, Pascale J.M., Hoorn, Sanne Ten, Tan, Miaomiao, He, Lingli, van Hooff, Sander R., Koster, Jan, Nijman, Lisanne E., Vink, Geraldine R., Beumer, Inès J., Elbers, Clara C., Lenos, Kristiaan J., Sommeijer, Dirkje W., Wang, Xin, and Vermeulen, Louis

Published
2024

8. Erratum: Correction: A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues (Life science alliance (2024) 7 8 PII: e202402889 DOI: 10.26508/lsa.202402730)

Author

Cancer, Onderzoek Medische Oncologie, Medisch Oncologische Disciplines, de Back, Tim R., Wu, Tan, Schafrat, Pascale Jm, Ten Hoorn, Sanne, Tan, Miaomiao, He, Lingli, van Hooff, Sander R., Koster, Jan, Nijman, Lisanne E., Vink, Geraldine R., Beumer, Inès J., Elbers, Clara C., Lenos, Kristiaan J., Sommeijer, Dirkje W., Wang, Xin, Vermeulen, Louis, Cancer, Onderzoek Medische Oncologie, Medisch Oncologische Disciplines, de Back, Tim R., Wu, Tan, Schafrat, Pascale Jm, Ten Hoorn, Sanne, Tan, Miaomiao, He, Lingli, van Hooff, Sander R., Koster, Jan, Nijman, Lisanne E., Vink, Geraldine R., Beumer, Inès J., Elbers, Clara C., Lenos, Kristiaan J., Sommeijer, Dirkje W., Wang, Xin, and Vermeulen, Louis

Published
2024

9. Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases

Author

Lab Translational Oncology, Dienst Geestelijke Verzorging, Heelkunde Opleiding, Genetica, CMM Groep Cuppen, Cancer, Regenerative Medicine and Stem Cells, Bootsma, Sanne, Dings, Mark P.G., Kesselaar, Job, Helderman, Roxan F.C.P.A., van Megesen, Kyah, Constantinides, Alexander, Moreno, Leandro Ferreira, Stelloo, Ellen, Scutigliani, Enzo M., Bokan, Bella, Torang, Arezo, van Hooff, Sander R., Zwijnenburg, Danny A., Wouters, Valérie M., van de Vlasakker, Vincent C.J., Galanos, Laskarina J.K., Nijman, Lisanne E., Logiantara, Adrian, Veenstra, Veronique L., Schlingemann, Sophie, van Piggelen, Sterre, van der Wel, Nicole, Krawczyk, Przemek M., Platteeuw, Johannes J., Tuynman, Jurriaan B., de Hingh, Ignace H., Klomp, Jan P.G., Oubrie, Arthur, Snaebjornsson, Petur, Medema, Jan Paul, Oei, Arlene L., Kranenburg, Onno, Elbers, Clara C., Lenos, Kristiaan J., Vermeulen, Louis, Bijlsma, Maarten F., Lab Translational Oncology, Dienst Geestelijke Verzorging, Heelkunde Opleiding, Genetica, CMM Groep Cuppen, Cancer, Regenerative Medicine and Stem Cells, Bootsma, Sanne, Dings, Mark P.G., Kesselaar, Job, Helderman, Roxan F.C.P.A., van Megesen, Kyah, Constantinides, Alexander, Moreno, Leandro Ferreira, Stelloo, Ellen, Scutigliani, Enzo M., Bokan, Bella, Torang, Arezo, van Hooff, Sander R., Zwijnenburg, Danny A., Wouters, Valérie M., van de Vlasakker, Vincent C.J., Galanos, Laskarina J.K., Nijman, Lisanne E., Logiantara, Adrian, Veenstra, Veronique L., Schlingemann, Sophie, van Piggelen, Sterre, van der Wel, Nicole, Krawczyk, Przemek M., Platteeuw, Johannes J., Tuynman, Jurriaan B., de Hingh, Ignace H., Klomp, Jan P.G., Oubrie, Arthur, Snaebjornsson, Petur, Medema, Jan Paul, Oei, Arlene L., Kranenburg, Onno, Elbers, Clara C., Lenos, Kristiaan J., Vermeulen, Louis, and Bijlsma, Maarten F.

Published
2024

10. Comparison Between Southern Blots and qPCR Analysis of Leukocyte Telomere Length in the Health ABC Study

Author

Elbers, Clara C, Garcia, Melissa E, Kimura, Masayuki, Cummings, Steven R, Nalls, Mike A, Newman, Anne B, Park, Vicki, Sanders, Jason L, Tranah, Gregory J, Tishkoff, Sarah A, Harris, Tamara B, and Aviv, Abraham

Subjects
Aging, Black or African American, Aged, Blotting, Southern, Body Composition, Female, Humans, Leukocytes, Male, Real-Time Polymerase Chain Reaction, Telomere, White People, Leukocyte telomere length, Quantitative PCR, Southern blots., Clinical Sciences, Gerontology
Abstract

Only a few studies, primarily limited to small samples, have examined the relationship between leukocyte telomere length (LTL) data generated by Southern blots, expressed in kilobases, versus quantitative PCR data, expressed in the telomere product/a single gene product (T/S). In the present study, we compared LTL data generated by the two methods in 681 elderly participants (50% African Americans, 50% of European origin, 49.2% women, mean age 73.7±2.9 years) in the Health Aging and Body Composition Study. The correlation between the data generated by the two methods was modest (R (2) = .27). Both methods captured the age effect on LTL and the longer LTL in women than in men. However, only the Southern blot method showed a significantly longer LTL in African Americans than in European decent individuals, which might be attributed to the larger measurement error of the quantitative PCR-based method than the Southern blots.

Published
2014

11. Loci influencing blood pressure identified using a cardiovascular gene-centric array

Author

Ganesh, Santhi K, Tragante, Vinicius, Guo, Wei, Guo, Yiran, Lanktree, Matthew B, Smith, Erin N, Johnson, Toby, Castillo, Berta Almoguera, Barnard, John, Baumert, Jens, Chang, Yen-Pei Christy, Elbers, Clara C, Farrall, Martin, Fischer, Mary E, Franceschini, Nora, Gaunt, Tom R, Gho, Johannes MIH, Gieger, Christian, Gong, Yan, Isaacs, Aaron, Kleber, Marcus E, Leach, Irene Mateo, McDonough, Caitrin W, Meijs, Matthijs FL, Mellander, Olle, Molony, Cliona M, Nolte, Ilja M, Padmanabhan, Sandosh, Price, Tom S, Rajagopalan, Ramakrishnan, Shaffer, Jonathan, Shah, Sonia, Shen, Haiqing, Soranzo, Nicole, van der Most, Peter J, Van Iperen, Erik PA, Van Setten, Jessic A, Vonk, Judith M, Zhang, Li, Beitelshees, Amber L, Berenson, Gerald S, Bhatt, Deepak L, Boer, Jolanda MA, Boerwinkle, Eric, Burkley, Ben, Burt, Amber, Chakravarti, Aravinda, Chen, Wei, Cooper-DeHoff, Rhonda M, Curtis, Sean P, Dreisbach, Albert, Duggan, David, Ehret, Georg B, Fabsitz, Richard R, Fornage, Myriam, Fox, Ervin, Furlong, Clement E, Gansevoort, Ron T, Hofker, Marten H, Hovingh, G Kees, Kirkland, Susan A, Kottke-Marchant, Kandice, Kutlar, Abdullah, LaCroix, Andrea Z, Langaee, Taimour Y, Li, Yun R, Lin, Honghuang, Liu, Kiang, Maiwald, Steffi, Malik, Rainer, Murugesan, Gurunathan, Newton-Cheh, Christopher, O'Connell, Jeffery R, Onland-Moret, N Charlotte, Ouwehand, Willem H, Palmas, Walter, Penninx, Brenda W, Pepine, Carl J, Pettinger, Mary, Polak, Joseph F, Ramachandran, Vasan S, Ranchalis, Jane, Redline, Susan, Ridker, Paul M, Rose, Lynda M, Scharnag, Hubert, Schork, Nicholas J, Shimbo, Daichi, Shuldiner, Alan R, Srinivasan, Sathanur R, Stolk, Ronald P, Taylor, Herman A, Thorand, Barbara, Trip, Mieke D, van Duijn, Cornelia M, Verschuren, W Monique, Wijmenga, Cisca, Winkelmann, Bernhard R, Wyatt, Sharon, and Young, J Hunter

Subjects
Hypertension, Heart Disease, Human Genome, Genetics, Clinical Research, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Blood Pressure, Cardiovascular Diseases, Chromosome Mapping, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, White People, CARDIOGRAM, METASTROKE, LifeLines Cohort Study, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

Published
2013

12. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans

Author

Mangino, Massimo, Hwang, Shih-Jen, Spector, Timothy D, Hunt, Steven C, Kimura, Masayuki, Fitzpatrick, Annette L, Christiansen, Lene, Petersen, Inge, Elbers, Clara C, Harris, Tamara, Chen, Wei, Srinivasan, Sathanur R, Kark, Jeremy D, Benetos, Athanase, Shamieh, Said El, Visvikis-Siest, Sophie, Christensen, Kaare, Berenson, Gerald S, Valdes, Ana M, Viñuela, Ana, Garcia, Melissa, Arnett, Donna K, Broeckel, Ulrich, Province, Michael A, Pankow, James S, Kammerer, Candace, Liu, Yongmei, Nalls, Michael, Tishkoff, Sarah, Thomas, Fridtjof, Ziv, Elad, Psaty, Bruce M, Bis, Joshua C, Rotter, Jerome I, Taylor, Kent D, Smith, Erin, Schork, Nicholas J, Levy, Daniel, and Aviv, Abraham

Subjects
Biological Sciences, Genetics, Aging, Human Genome, 2.1 Biological and endogenous factors, Generic health relevance, Genome-Wide Association Study, Humans, Kruppel-Like Transcription Factors, Telomere, Telomere Homeostasis, Telomere-Binding Proteins, Medical and Health Sciences, Genetics & Heredity
Abstract

Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10(-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

Published
2012

13. Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Author

Elbers, Clara C, Guo, Yiran, Tragante, Vinicius, van Iperen, Erik PA, Lanktree, Matthew B, Castillo, Berta Almoguera, Chen, Fang, Yanek, Lisa R, Wojczynski, Mary K, Li, Yun R, Ferwerda, Bart, Ballantyne, Christie M, Buxbaum, Sarah G, Chen, Yii-Der Ida, Chen, Wei-Min, Cupples, L Adrienne, Cushman, Mary, Duan, Yanan, Duggan, David, Evans, Michele K, Fernandes, Jyotika K, Fornage, Myriam, Garcia, Melissa, Garvey, W Timothy, Glazer, Nicole, Gomez, Felicia, Harris, Tamara B, Halder, Indrani, Howard, Virginia J, Keller, Margaux F, Kamboh, M Ilyas, Kooperberg, Charles, Kritchevsky, Stephen B, LaCroix, Andrea, Liu, Kiang, Liu, Yongmei, Musunuru, Kiran, Newman, Anne B, Onland-Moret, N Charlotte, Ordovas, Jose, Peter, Inga, Post, Wendy, Redline, Susan, Reis, Steven E, Saxena, Richa, Schreiner, Pamela J, Volcik, Kelly A, Wang, Xingbin, Yusuf, Salim, Zonderland, Alan B, Anand, Sonia S, Becker, Diane M, Psaty, Bruce, Rader, Daniel J, Reiner, Alex P, Rich, Stephen S, Rotter, Jerome I, Sale, Michèle M, Tsai, Michael Y, Borecki, Ingrid B, Hegele, Robert A, Kathiresan, Sekar, Nalls, Michael A, Taylor, Herman A, Hakonarson, Hakon, Sivapalaratnam, Suthesh, Asselbergs, Folkert W, Drenos, Fotios, Wilson, James G, and Keating, Brendan J

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Atherosclerosis, Health Disparities, Minority Health, Metabolic and endocrine, Alleles, Asian People, Black People, Cholesterol, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Hispanic or Latino, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Polymorphism, Single Nucleotide, Triglycerides, Black or African American, genetic variants, loci, lipid, genotyping, CD36 deficiency, General Science & Technology
Abstract

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

Published
2012

14. Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA.

Author

Fehrmann, Rudolf SN, Jansen, Ritsert C, Veldink, Jan H, Westra, Harm-Jan, Arends, Danny, Bonder, Marc Jan, Fu, Jingyuan, Deelen, Patrick, Groen, Harry JM, Smolonska, Asia, Weersma, Rinse K, Hofstra, Robert MW, Buurman, Wim A, Rensen, Sander, Wolfs, Marcel GM, Platteel, Mathieu, Zhernakova, Alexandra, Elbers, Clara C, Festen, Eleanora M, Trynka, Gosia, Hofker, Marten H, Saris, Christiaan GJ, Ophoff, Roel A, van den Berg, Leonard H, van Heel, David A, Wijmenga, Cisca, Te Meerman, Gerard J, and Franke, Lude

Subjects
Monocytes, Humans, HLA Antigens, Chromosome Mapping, Gene Expression Profiling, Gene Expression Regulation, Genotype, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genetic Variation, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

For many complex traits, genetic variants have been found associated. However, it is still mostly unclear through which downstream mechanism these variants cause these phenotypes. Knowledge of these intermediate steps is crucial to understand pathogenesis, while also providing leads for potential pharmacological intervention. Here we relied upon natural human genetic variation to identify effects of these variants on trans-gene expression (expression quantitative trait locus mapping, eQTL) in whole peripheral blood from 1,469 unrelated individuals. We looked at 1,167 published trait- or disease-associated SNPs and observed trans-eQTL effects on 113 different genes, of which we replicated 46 in monocytes of 1,490 different individuals and 18 in a smaller dataset that comprised subcutaneous adipose, visceral adipose, liver tissue, and muscle tissue. HLA single-nucleotide polymorphisms (SNPs) were 10-fold enriched for trans-eQTLs: 48% of the trans-acting SNPs map within the HLA, including ulcerative colitis susceptibility variants that affect plausible candidate genes AOAH and TRBV18 in trans. We identified 18 pairs of unlinked SNPs associated with the same phenotype and affecting expression of the same trans-gene (21 times more than expected, P

Published
2011

15. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

Author

Lanktree, Matthew B, Guo, Yiran, Murtaza, Muhammed, Glessner, Joseph T, Bailey, Swneke D, Onland-Moret, N Charlotte, Lettre, Guillaume, Ongen, Halit, Rajagopalan, Ramakrishnan, Johnson, Toby, Shen, Haiqing, Nelson, Christopher P, Klopp, Norman, Baumert, Jens, Padmanabhan, Sandosh, Pankratz, Nathan, Pankow, James S, Shah, Sonia, Taylor, Kira, Barnard, John, Peters, Bas J, Maloney, Cliona M, Lobmeyer, Maximilian T, Stanton, Alice, Zafarmand, M Hadi, Romaine, Simon PR, Mehta, Amar, van Iperen, Erik PA, Gong, Yan, Price, Tom S, Smith, Erin N, Kim, Cecilia E, Li, Yun R, Asselbergs, Folkert W, Atwood, Larry D, Bailey, Kristian M, Bhatt, Deepak, Bauer, Florianne, Behr, Elijah R, Bhangale, Tushar, Boer, Jolanda MA, Boehm, Bernhard O, Bradfield, Jonathan P, Brown, Morris, Braund, Peter S, Burton, Paul R, Carty, Cara, Chandrupatla, Hareesh R, Chen, Wei, Connell, John, Dalgeorgou, Chrysoula, de Boer, Anthonius, Drenos, Fotios, Elbers, Clara C, Fang, James C, Fox, Caroline S, Frackelton, Edward C, Fuchs, Barry, Furlong, Clement E, Gibson, Quince, Gieger, Christian, Goel, Anuj, Grobbee, Diederik E, Hastie, Claire, Howard, Philip J, Huang, Guan-Hua, Johnson, W Craig, Li, Qing, Kleber, Marcus E, Klein, Barbara EK, Klein, Ronald, Kooperberg, Charles, Ky, Bonnie, LaCroix, Andrea, Lanken, Paul, Lathrop, Mark, Li, Mingyao, Marshall, Vanessa, Melander, Olle, Mentch, Frank D, Meyer, Nuala J, Monda, Keri L, Montpetit, Alexandre, Murugesan, Gurunathan, Nakayama, Karen, Nondahl, Dave, Onipinla, Abiodun, Rafelt, Suzanne, Newhouse, Stephen J, Otieno, F George, Patel, Sanjey R, Putt, Mary E, Rodriguez, Santiago, Safa, Radwan N, Sawyer, Douglas B, Schreiner, Pamela J, Simpson, Claire, Sivapalaratnam, Suthesh, Srinivasan, Sathanur R, and Suver, Christine

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Black or African American, Asian People, Body Height, Cardiovascular System, Female, Gene Frequency, Genetic Heterogeneity, Genetic Loci, Genome-Wide Association Study, Hispanic or Latino, Humans, Interleukin-11, Male, Polymorphism, Single Nucleotide, Smad3 Protein, White People, Hugh Watkins on behalf of PROCARDIS, Meena Kumari on behalf of the Whitehall II Study and the WHII 50K Group, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.

Published
2011

17. Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci

Author

Tragante, Vinicius, Barnes, Michael R., Ganesh, Santhi K., Lanktree, Matthew B., Guo, Wei, Franceschini, Nora, Smith, Erin N., Johnson, Toby, Holmes, Michael V., Padmanabhan, Sandosh, Karczewski, Konrad J., Almoguera, Berta, Barnard, John, Baumert, Jens, Chang, Yen-Pei Christy, Elbers, Clara C., Farrall, Martin, Fischer, Mary E., Gaunt, Tom R., Gho, Johannes M.I.H., Gieger, Christian, Goel, Anuj, Gong, Yan, Isaacs, Aaron, Kleber, Marcus E., Leach, Irene Mateo, McDonough, Caitrin W., Meijs, Matthijs F.L., Melander, Olle, Nelson, Christopher P., Nolte, Ilja M., Pankratz, Nathan, Price, Tom S., Shaffer, Jonathan, Shah, Sonia, Tomaszewski, Maciej, van der Most, Peter J., Van Iperen, Erik P.A., Vonk, Judith M., Witkowska, Kate, Wong, Caroline O.L., Zhang, Li, Beitelshees, Amber L., Berenson, Gerald S., Bhatt, Deepak L., Brown, Morris, Burt, Amber, Cooper-DeHoff, Rhonda M., Connell, John M., Cruickshanks, Karen J., Curtis, Sean P., Davey-Smith, George, Delles, Christian, Gansevoort, Ron T., Guo, Xiuqing, Haiqing, Shen, Hastie, Claire E., Hofker, Marten H., Hovingh, G. Kees, Kim, Daniel S., Kirkland, Susan A., Klein, Barbara E., Klein, Ronald, Li, Yun R., Maiwald, Steffi, Newton-Cheh, Christopher, O’Brien, Eoin T., Onland-Moret, N. Charlotte, Palmas, Walter, Parsa, Afshin, Penninx, Brenda W., Pettinger, Mary, Vasan, Ramachandran S., Ranchalis, Jane E., M Ridker, Paul, Rose, Lynda M., Sever, Peter, Shimbo, Daichi, Steele, Laura, Stolk, Ronald P., Thorand, Barbara, Trip, Mieke D., van Duijn, Cornelia M., Verschuren, W. Monique, Wijmenga, Cisca, Wyatt, Sharon, Young, J. Hunter, Zwinderman, Aeilko H., Bezzina, Connie R., Boerwinkle, Eric, Casas, Juan P., Caulfield, Mark J., Chakravarti, Aravinda, Chasman, Daniel I., Davidson, Karina W., Doevendans, Pieter A., Dominiczak, Anna F., FitzGerald, Garret A., Gums, John G., Fornage, Myriam, Hakonarson, Hakon, Halder, Indrani, Hillege, Hans L., Illig, Thomas, Jarvik, Gail P., Johnson, Julie A., Kastelein, John J.P., Koenig, Wolfgang, Kumari, Meena, März, Winfried, Murray, Sarah S., O’Connell, Jeffery R., Oldehinkel, Albertine J., Pankow, James S., Rader, Daniel J., Redline, Susan, Reilly, Muredach P., Schadt, Eric E., Kottke-Marchant, Kandice, Snieder, Harold, Snyder, Michael, Stanton, Alice V., Tobin, Martin D., Uitterlinden, André G., van der Harst, Pim, van der Schouw, Yvonne T., Samani, Nilesh J., Watkins, Hugh, Johnson, Andrew D., Reiner, Alex P., Zhu, Xiaofeng, de Bakker, Paul I.W., Levy, Daniel, Asselbergs, Folkert W., Munroe, Patricia B., and Keating, Brendan J.

Published
2014
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18. Causal Effects of Body Mass Index on Cardiometabolic Traits and Events: A Mendelian Randomization Analysis

Author

Holmes, Michael V., Lange, Leslie A., Palmer, Tom, Lanktree, Matthew B., North, Kari E., Almoguera, Berta, Buxbaum, Sarah, Chandrupatla, Hareesh R., Elbers, Clara C., Guo, Yiran, Hoogeveen, Ron C., Li, Jin, Li, Yun R., Swerdlow, Daniel I., Cushman, Mary, Price, Tom S., Curtis, Sean P., Fornage, Myriam, Hakonarson, Hakon, Patel, Sanjay R., Redline, Susan, Siscovick, David S., Tsai, Michael Y., Wilson, James G., van der Schouw, Yvonne T., FitzGerald, Garret A., Hingorani, Aroon D., Casas, Juan P., de Bakker, Paul I.W., Rich, Stephen S., Schadt, Eric E., Asselbergs, Folkert W., Reiner, Alex P., and Keating, Brendan J.

Published
2014
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19. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Author

Asselbergs, Folkert W., Guo, Yiran, van Iperen, Erik P.A., Sivapalaratnam, Suthesh, Tragante, Vinicius, Lanktree, Matthew B., Lange, Leslie A., Almoguera, Berta, Appelman, Yolande E., Barnard, John, Baumert, Jens, Beitelshees, Amber L., Bhangale, Tushar R., Chen, Yii-Der Ida, Gaunt, Tom R., Gong, Yan, Hopewell, Jemma C., Johnson, Toby, Kleber, Marcus E., Langaee, Taimour Y., Li, Mingyao, Li, Yun R., Liu, Kiang, McDonough, Caitrin W., Meijs, Matthijs F.L., Middelberg, Rita P.S., Musunuru, Kiran, Nelson, Christopher P., O’Connell, Jeffery R., Padmanabhan, Sandosh, Pankow, James S., Pankratz, Nathan, Rafelt, Suzanne, Rajagopalan, Ramakrishnan, Romaine, Simon P.R., Schork, Nicholas J., Shaffer, Jonathan, Shen, Haiqing, Smith, Erin N., Tischfield, Sam E., van der Most, Peter J., van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Volcik, Kelly A., Zhang, Li, Bailey, Kent R., Bailey, Kristian M., Bauer, Florianne, Boer, Jolanda M.A., Braund, Peter S., Burt, Amber, Burton, Paul R., Buxbaum, Sarah G., Chen, Wei, Cooper-DeHoff, Rhonda M., Cupples, L. Adrienne, deJong, Jonas S., Delles, Christian, Duggan, David, Fornage, Myriam, Furlong, Clement E., Glazer, Nicole, Gums, John G., Hastie, Claire, Holmes, Michael V., Illig, Thomas, Kirkland, Susan A., Kivimaki, Mika, Klein, Ronald, Klein, Barbara E., Kooperberg, Charles, Kottke-Marchant, Kandice, Kumari, Meena, LaCroix, Andrea Z., Mallela, Laya, Murugesan, Gurunathan, Ordovas, Jose, Ouwehand, Willem H., Post, Wendy S., Saxena, Richa, Scharnagl, Hubert, Schreiner, Pamela J., Shah, Tina, Shields, Denis C., Shimbo, Daichi, Srinivasan, Sathanur R., Stolk, Ronald P., Swerdlow, Daniel I., Taylor, Herman A., Jr., Topol, Eric J., Toskala, Elina, van Pelt, Joost L., van Setten, Jessica, Yusuf, Salim, Whittaker, John C., Zwinderman, A.H., Anand, Sonia S., Balmforth, Anthony J., Berenson, Gerald S., Bezzina, Connie R., Boehm, Bernhard O., Boerwinkle, Eric, Casas, Juan P., Caulfield, Mark J., Clarke, Robert, Connell, John M., Cruickshanks, Karen J., Davidson, Karina W., Day, Ian N.M., de Bakker, Paul I.W., Doevendans, Pieter A., Dominiczak, Anna F., Hall, Alistair S., Hartman, Catharina A., Hengstenberg, Christian, Hillege, Hans L., Hofker, Marten H., Humphries, Steve E., Jarvik, Gail P., Johnson, Julie A., Kaess, Bernhard M., Kathiresan, Sekar, Koenig, Wolfgang, Lawlor, Debbie A., März, Winfried, Melander, Olle, Mitchell, Braxton D., Montgomery, Grant W., Munroe, Patricia B., Murray, Sarah S., Newhouse, Stephen J., Onland-Moret, N. Charlotte, Poulter, Neil, Psaty, Bruce, Redline, Susan, Rich, Stephen S., Rotter, Jerome I., Schunkert, Heribert, Sever, Peter, Shuldiner, Alan R., Silverstein, Roy L., Stanton, Alice, Thorand, Barbara, Trip, Mieke D., Tsai, Michael Y., van der Harst, Pim, van der Schoot, Ellen, van der Schouw, Yvonne T., Verschuren, W.M. Monique, Watkins, Hugh, Wilde, Arthur A.M., Wolffenbuttel, Bruce H.R., Whitfield, John B., Hovingh, G. Kees, Ballantyne, Christie M., Wijmenga, Cisca, Reilly, Muredach P., Martin, Nicholas G., Wilson, James G., Rader, Daniel J., Samani, Nilesh J., Reiner, Alex P., Hegele, Robert A., Kastelein, John J.P., Hingorani, Aroon D., Talmud, Philippa J., Hakonarson, Hakon, Elbers, Clara C., Keating, Brendan J., and Drenos, Fotios

Published
2012
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20. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study

Author

Voight, Benjamin F, Peloso, Gina M, Orho-Melander, Marju, Frikke-Schmidt, Ruth, Barbalic, Maja, Jensen, Majken K, Hindy, George, Hólm, Hilma, Ding, Eric L, Johnson, Toby, Schunkert, Heribert, Samani, Nilesh J, Clarke, Robert, Hopewell, Jemma C, Thompson, John F, Li, Mingyao, Thorleifsson, Gudmar, Newton-Cheh, Christopher, Musunuru, Kiran, Pirruccello, James P, Saleheen, Danish, Chen, Li, Stewart, Alexandre FR, Schillert, Arne, Thorsteinsdottir, Unnur, Thorgeirsson, Gudmundur, Anand, Sonia, Engert, James C, Morgan, Thomas, Spertus, John, Stoll, Monika, Berger, Klaus, Martinelli, Nicola, Girelli, Domenico, McKeown, Pascal P, Patterson, Christopher C, Epstein, Stephen E, Devaney, Joseph, Burnett, Mary-Susan, Mooser, Vincent, Ripatti, Samuli, Surakka, Ida, Nieminen, Markku S, Sinisalo, Juha, Lokki, Marja-Liisa, Perola, Markus, Havulinna, Aki, de Faire, Ulf, Gigante, Bruna, Ingelsson, Erik, Zeller, Tanja, Wild, Philipp, de Bakker, Paul I W, Klungel, Olaf H, Maitland-van der Zee, Anke-Hilse, Peters, Bas J M, de Boer, Anthonius, Grobbee, Diederick E, Kamphuisen, Pieter W, Deneer, Vera H M, Elbers, Clara C, Onland-Moret, N Charlotte, Hofker, Marten H, Wijmenga, Cisca, Verschuren, WM Monique, Boer, Jolanda MA, van der Schouw, Yvonne T, Rasheed, Asif, Frossard, Philippe, Demissie, Serkalem, Willer, Cristen, Do, Ron, Ordovas, Jose M, Abecasis, Gonçalo R, Boehnke, Michael, Mohlke, Karen L, Daly, Mark J, Guiducci, Candace, Burtt, Noël P, Surti, Aarti, Gonzalez, Elena, Purcell, Shaun, Gabriel, Stacey, Marrugat, Jaume, Peden, John, Erdmann, Jeanette, Diemert, Patrick, Willenborg, Christina, König, Inke R, Fischer, Marcus, Hengstenberg, Christian, Ziegler, Andreas, Buysschaert, Ian, Lambrechts, Diether, Van de Werf, Frans, Fox, Keith A, El Mokhtari, Nour Eddine, Rubin, Diana, Schrezenmeir, Jürgen, Schreiber, Stefan, Schäfer, Arne, Danesh, John, Blankenberg, Stefan, Roberts, Robert, McPherson, Ruth, Watkins, Hugh, Hall, Alistair S, Overvad, Kim, Rimm, Eric, Boerwinkle, Eric, Tybjaerg-Hansen, Anne, Cupples, L Adrienne, Reilly, Muredach P, Melander, Olle, Mannucci, Pier M, Ardissino, Diego, Siscovick, David, Elosua, Roberto, Stefansson, Kari, O'Donnell, Christopher J, Salomaa, Veikko, Rader, Daniel J, Peltonen, Leena, Schwartz, Stephen M, Altshuler, David, and Kathiresan, Sekar

Published
2012
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22. Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

Author

Saxena, Richa, Elbers, Clara C., Guo, Yiran, Peter, Inga, Gaunt, Tom R., Mega, Jessica L., Lanktree, Matthew B., Tare, Archana, Castillo, Berta Almoguera, Li, Yun R., Johnson, Toby, Bruinenberg, Marcel, Gilbert-Diamond, Diane, Rajagopalan, Ramakrishnan, Voight, Benjamin F., Balasubramanyam, Ashok, Barnard, John, Bauer, Florianne, Baumert, Jens, Bhangale, Tushar, Böhm, Bernhard O., Braund, Peter S., Burton, Paul R., Chandrupatla, Hareesh R., Clarke, Robert, Cooper-DeHoff, Rhonda M., Crook, Errol D., Davey-Smith, George, Day, Ian N., de Boer, Anthonius, de Groot, Mark C.H., Drenos, Fotios, Ferguson, Jane, Fox, Caroline S., Furlong, Clement E., Gibson, Quince, Gieger, Christian, Gilhuijs-Pederson, Lisa A., Glessner, Joseph T., Goel, Anuj, Gong, Yan, Grant, Struan F.A., Grobbee, Diederick E., Hastie, Claire, Humphries, Steve E., Kim, Cecilia E., Kivimaki, Mika, Kleber, Marcus, Meisinger, Christa, Kumari, Meena, Langaee, Taimour Y., Lawlor, Debbie A., Li, Mingyao, Lobmeyer, Maximilian T., Maitland-van der Zee, Anke-Hilse, Meijs, Matthijs F.L., Molony, Cliona M., Morrow, David A., Murugesan, Gurunathan, Musani, Solomon K., Nelson, Christopher P., Newhouse, Stephen J., O'Connell, Jeffery R., Padmanabhan, Sandosh, Palmen, Jutta, Patel, Sanjey R., Pepine, Carl J., Pettinger, Mary, Price, Thomas S., Rafelt, Suzanne, Ranchalis, Jane, Rasheed, Asif, Rosenthal, Elisabeth, Ruczinski, Ingo, Shah, Sonia, Shen, Haiqing, Silbernagel, Günther, Smith, Erin N., Spijkerman, Annemieke W.M., Stanton, Alice, Steffes, Michael W., Thorand, Barbara, Trip, Mieke, van der Harst, Pim, van der A, Daphne L., van Iperen, Erik P.A., van Setten, Jessica, van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Wolffenbuttel, Bruce H.R., Young, Taylor, Zafarmand, M. Hadi, Zmuda, Joseph M., Boehnke, Michael, Altshuler, David, McCarthy, Mark, Kao, W.H. Linda, Pankow, James S., Cappola, Thomas P., Sever, Peter, Poulter, Neil, Caulfield, Mark, Dominiczak, Anna, Shields, Denis C., Bhatt, Deepak L., Zhang, Li, Curtis, Sean P., Danesh, John, Casas, Juan P., van der Schouw, Yvonne T., Onland-Moret, N. Charlotte, Doevendans, Pieter A., Dorn, Gerald W., II, Farrall, Martin, FitzGerald, Garret A., Hamsten, Anders, Hegele, Robert, Hingorani, Aroon D., Hofker, Marten H., Huggins, Gordon S., Illig, Thomas, Jarvik, Gail P., Johnson, Julie A., Klungel, Olaf H., Knowler, William C., Koenig, Wolfgang, März, Winfried, Meigs, James B., Melander, Olle, Munroe, Patricia B., Mitchell, Braxton D., Bielinski, Susan J., Rader, Daniel J., Reilly, Muredach P., Rich, Stephen S., Rotter, Jerome I., Saleheen, Danish, Samani, Nilesh J., Schadt, Eric E., Shuldiner, Alan R., Silverstein, Roy, Kottke-Marchant, Kandice, Talmud, Philippa J., Watkins, Hugh, Asselbergs, Folkert W., de Bakker, Paul I.W., McCaffery, Jeanne, Wijmenga, Cisca, Sabatine, Marc S., Wilson, James G., Reiner, Alex, Bowden, Donald W., Hakonarson, Hakon, Siscovick, David S., and Keating, Brendan J.

Published
2012
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23. Molecular characterization of colorectal cancer related peritoneal metastatic disease

Author

Lenos, Kristiaan J, Bach, Sander, Ferreira Moreno, Leandro, Ten Hoorn, Sanne, Sluiter, Nina R, Bootsma, Sanne, Vieira Braga, Felipe A, Nijman, Lisanne E, van den Bosch, Tom, Miedema, Daniel M, van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P, Stransky, Nicolas, Smolen, Gromoslaw A, Coebergh van den Braak, Robert R J, IJzermans, Jan N M, Martens, John W M, Hallam, Sally, Beggs, Andrew D, Kops, Geert J P L, Lansu, Nico, Bastiaenen, Vivian P, Klaver, Charlotte E L, Lecca, Maria C, El Makrini, Khalid, Elbers, Clara C, Dings, Mark P G, van Noesel, Carel J M, Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J A, Tanis, Pieter J, de Hingh, Ignace H, Bijlsma, Maarten F, Tuynman, Jurriaan B, Vermeulen, Louis, Lenos, Kristiaan J, Bach, Sander, Ferreira Moreno, Leandro, Ten Hoorn, Sanne, Sluiter, Nina R, Bootsma, Sanne, Vieira Braga, Felipe A, Nijman, Lisanne E, van den Bosch, Tom, Miedema, Daniel M, van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P, Stransky, Nicolas, Smolen, Gromoslaw A, Coebergh van den Braak, Robert R J, IJzermans, Jan N M, Martens, John W M, Hallam, Sally, Beggs, Andrew D, Kops, Geert J P L, Lansu, Nico, Bastiaenen, Vivian P, Klaver, Charlotte E L, Lecca, Maria C, El Makrini, Khalid, Elbers, Clara C, Dings, Mark P G, van Noesel, Carel J M, Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J A, Tanis, Pieter J, de Hingh, Ignace H, Bijlsma, Maarten F, Tuynman, Jurriaan B, and Vermeulen, Louis

Abstract

A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.

Published
2022

24. Molecular characterization of colorectal cancer related peritoneal metastatic disease

Author

CMM, Cancer, Hubrecht Institute with UMC, Heelkundig Oncologische Disciplines, Lab Translational Oncology, Regenerative Medicine and Stem Cells, Lenos, Kristiaan J., Bach, Sander, Ferreira Moreno, Leandro, ten Hoorn, Sanne, Sluiter, Nina R., Bootsma, Sanne, Vieira Braga, Felipe A., Nijman, Lisanne E., van den Bosch, Tom, Miedema, Daniel M., van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P., Stransky, Nicolas, Smolen, Gromoslaw A., Coebergh van den Braak, Robert R.J., IJzermans, Jan N.M., Martens, John W.M., Hallam, Sally, Beggs, Andrew D., Kops, Geert J.P.L., Lansu, Nico, Bastiaenen, Vivian P., Klaver, Charlotte E.L., Lecca, Maria C., El Makrini, Khalid, Elbers, Clara C., Dings, Mark P.G., van Noesel, Carel J.M., Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J.A., Tanis, Pieter J., de Hingh, Ignace H., Bijlsma, Maarten F., Tuynman, Jurriaan B., Vermeulen, Louis, CMM, Cancer, Hubrecht Institute with UMC, Heelkundig Oncologische Disciplines, Lab Translational Oncology, Regenerative Medicine and Stem Cells, Lenos, Kristiaan J., Bach, Sander, Ferreira Moreno, Leandro, ten Hoorn, Sanne, Sluiter, Nina R., Bootsma, Sanne, Vieira Braga, Felipe A., Nijman, Lisanne E., van den Bosch, Tom, Miedema, Daniel M., van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P., Stransky, Nicolas, Smolen, Gromoslaw A., Coebergh van den Braak, Robert R.J., IJzermans, Jan N.M., Martens, John W.M., Hallam, Sally, Beggs, Andrew D., Kops, Geert J.P.L., Lansu, Nico, Bastiaenen, Vivian P., Klaver, Charlotte E.L., Lecca, Maria C., El Makrini, Khalid, Elbers, Clara C., Dings, Mark P.G., van Noesel, Carel J.M., Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J.A., Tanis, Pieter J., de Hingh, Ignace H., Bijlsma, Maarten F., Tuynman, Jurriaan B., and Vermeulen, Louis

Published
2022

28. Mendelian randomization of blood lipids for coronary heart disease

Author

Holmes, Michael V., Asselbergs, Folkert W., Palmer, Tom M., Drenos, Fotios, Lanktree, Matthew B., Nelson, Christopher P., Dale, Caroline E., Padmanabhan, Sandosh, Finan, Chris, Swerdlow, Daniel I., Tragante, Vinicius, van Iperen, Erik P.A., Sivapalaratnam, Suthesh, Shah, Sonia, Elbers, Clara C., Shah, Tina, Engmann, Jorgen, Giambartolomei, Claudia, White, Jon, Zabaneh, Delilah, Sofat, Reecha, McLachlan, Stela, Doevendans, Pieter A., Balmforth, Anthony J., Hall, Alistair S., North, Kari E., Almoguera, Berta, Hoogeveen, Ron C., Cushman, Mary, Fornage, Myriam, Patel, Sanjay R., Redline, Susan, Siscovick, David S., Tsai, Michael Y., Karczewski, Konrad J., Hofker, Marten H., Verschuren, W. Monique, Bots, Michiel L., van der Schouw, Yvonne T., Melander, Olle, Dominiczak, Anna F., Morris, Richard, Ben-Shlomo, Yoav, Price, Jackie, Kumari, Meena, Baumert, Jens, Peters, Annette, Thorand, Barbara, Koenig, Wolfgang, Gaunt, Tom R., Humphries, Steve E., Clarke, Robert, Watkins, Hugh, Farrall, Martin, Wilson, James G., Rich, Stephen S., de Bakker, Paul I.W., Lange, Leslie A., Davey Smith, George, Reiner, Alex P., Talmud, Philippa J., Kivimäki, Mika, Lawlor, Debbie A., Dudbridge, Frank, Samani, Nilesh J., Keating, Brendan J., Hingorani, Aroon D., and Casas, Juan P.

Published
2015
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29. Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection

Author

Zhernakova, Alexandra, Elbers, Clara C., Ferwerda, Bart, Romanos, Jihane, Trynka, Gosia, Dubois, Patrick C., de Kovel, Carolien G.F., Franke, Lude, Oosting, Marije, Barisani, Donatella, Bardella, Maria Teresa, Joosten, Leo A.B., Saavalainen, Paivi, van Heel, David A., Catassi, Carlo, Netea, Mihai G., and Wijmenga, Cisca

Subjects
Bacterial infections -- Prevention, Celiac disease -- Genetic aspects, Celiac disease -- Research, Haplotypes -- Research, Lipopolysaccharides -- Health aspects, Biological sciences
Abstract

The integrated haplotype score method is employed for a complete evolutionary, as well as functional analysis of the risk loci of the celiac disease. The analyses prove that SH2B3 plays an extremely significant factor for protecting people against bacterial infection.

Published
2010

31. Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations

Author

Yoneyama, Sachiko, Guo, Yiran, Lanktree, Matthew B., Barnes, Michael R., Elbers, Clara C., Karczewski, Konrad J, Padmanabhan, Sandosh, Bauer, Florianne, Baumert, Jens, Beitelshees, Amber, Berenson, Gerald S., Boer, Jolanda M.A., Burke, Gregory, Cade, Brian, Chen, Wei, Cooper-Dehoff, Rhonda M., Gaunt, Tom R., Gieger, Christian, Gong, Yan, Gorski, Mathias, Heard-Costa, Nancy, Johnson, Toby, Lamonte, Michael J., Mcdonough, Caitrin, Monda, Keri L., Onland-Moret, Charlotte N., Nelson, Christopher P., OʼConnell, Jeffrey R., Ordovas, Jose, Peter, Inga, Peters, Annette, Shaffer, Jonathan, Shen, Haiqinq, Smith, Erin, Speilotes, Liz, Thomas, Fridtjof, Thorand, Barbara, Verschuren, Monique W. M., Anand, Sonia S., Dominiczak, Anna, Davidson, Karina W., Hegele, Robert A., Heid, Iris, Hofker, Marten H., Huggins, Gordon S., Illig, Thomas, Johnson, Julie A., Kirkland, Susan, König, Wolfgang, Langaee, Taimour Y., Mccaffery, Jeanne, Melander, Olle, Mitchell, Braxton D., Munroe, Patricia, Murray, Sarah S., Papanicolaou, George, Redline, Susan, Reilly, Muredach, Samani, Nilesh J., Schork, Nicholas J., Van Der Schouw, Yvonne T., Shimbo, Daichi, Shuldiner, Alan R., Tobin, Martin D., Wijmenga, Cisca, Yusuf, Salim, Hakonarson, Hakon, Lange, Leslie A., Demerath, Ellen W, Fox, Caroline S., North, Kari E, Reiner, Alex P., Keating, Brendan, and Taylor, Kira C.

Published
2014
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32. Human dectin-1 deficiency and mucocutaneous fungal infections

Author

Ferwerda, Bart, Ferwerda, Gerben, Plantinga, Theo S., Willment, Janet A., van Spriel, Annemiek B., Venselaar, Hanka, Elbers, Clara C., Johnson, Melissa D., Cambi, Alessandra, Huysamen, Cristal, Jacobs, Liesbeth, Jansen, Trees, Verheijen, Karlijn, Masthoff, Laury, Morre, Servaas A., Vriend, Gert, Williams, David L., Perfect, John R., Joosten, Leo A.B., Wijmenga, Cisca, van der Meer, Jos W.M., Adema, Gosse J., Kullberg, Bart Jan, Brown, Gordon D., and Netea, Mihai G.

Subjects
Mycoses -- Genetic aspects, Mycoses -- Prevention, Candidiasis, Vulvovaginal -- Diagnosis, Gene mutations -- Research
Abstract

The article discusses the specific role that human dectin-1 deficiency plays in the prevention of mucocutaneous fungal infections. The findings of the dectin-1 mutation in persons from Europe and Africa reveal that it is an ancient mutation that emerged more than 60,000 years ago and also that the infection is genetic.

Published
2009

37. WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene

Author

Nersisyan, Lilit, Nikoghosyan, Maria, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Elbers, Clara C., Kloosterman, Wigard P., van Setten, Jessica, Nijman, Isaac J., Renkens, Ivo, de Bakker, Paul I. W., van Dijk, Freerk, Neerincx, Pieter B. T., Deelen, Patrick, Kanterakis, Alexandros, Dijkstra, Martijn, Byelas, Heorhiy, van der Velde, K. Joeri, Platteel, Mathieu, Swertz, Morris A., Wijmenga, Cisca, Palamara, Pier Francesco, Pe'er, Itsik, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H., Beekman, Marian, de Craen, Anton J. M., Suchiman, H. Eka D., Slagboom, P. Eline, Guryev, Victor, Abdellaoui, Abdel, Hottenga, Jouke Jan, Kattenberg, Mathijs, Willemsen, Gonneke, Boomsma, Dorret I., van Leeuwen, Elisabeth M., Karssen, Lennart C., Amin, Najaf, Rivadeneira, Fernando, Isaacs, Aaron, Hofman, Albert, Uitterlinden, Andre G., van Duijn, Cornelia M., van Oven, Mannis, Kayser, Manfred, Vermaat, Martijn, Laros, Jeroen F. J., den Dunnen, Johan T., van Enckevort, David, Mei, Hailiang, Li, Mingkun, Stoneking, Mark, van Schaik, Barbera D. C., Bot, Jan, Marschall, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Estrada, Karol, McCarroll, Steven A., Sunyaev, Shamil R., Hormozdiari, Fereydoun, Koval, Vyacheslav, Medina-Gomez, Carolina, Oostra, Ben, Veldink, Jan H., van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., de Knijff, Peter, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Wang, Jun, Li, Ning, Cao, Sujie, Bovenberg, Jasper A., van Ommen, Gert-Jan B., Arakelyan, Arsen, Nersisyan, Lilit, Nikoghosyan, Maria, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Elbers, Clara C., Kloosterman, Wigard P., van Setten, Jessica, Nijman, Isaac J., Renkens, Ivo, de Bakker, Paul I. W., van Dijk, Freerk, Neerincx, Pieter B. T., Deelen, Patrick, Kanterakis, Alexandros, Dijkstra, Martijn, Byelas, Heorhiy, van der Velde, K. Joeri, Platteel, Mathieu, Swertz, Morris A., Wijmenga, Cisca, Palamara, Pier Francesco, Pe'er, Itsik, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H., Beekman, Marian, de Craen, Anton J. M., Suchiman, H. Eka D., Slagboom, P. Eline, Guryev, Victor, Abdellaoui, Abdel, Hottenga, Jouke Jan, Kattenberg, Mathijs, Willemsen, Gonneke, Boomsma, Dorret I., van Leeuwen, Elisabeth M., Karssen, Lennart C., Amin, Najaf, Rivadeneira, Fernando, Isaacs, Aaron, Hofman, Albert, Uitterlinden, Andre G., van Duijn, Cornelia M., van Oven, Mannis, Kayser, Manfred, Vermaat, Martijn, Laros, Jeroen F. J., den Dunnen, Johan T., van Enckevort, David, Mei, Hailiang, Li, Mingkun, Stoneking, Mark, van Schaik, Barbera D. C., Bot, Jan, Marschall, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Estrada, Karol, McCarroll, Steven A., Sunyaev, Shamil R., Hormozdiari, Fereydoun, Koval, Vyacheslav, Medina-Gomez, Carolina, Oostra, Ben, Veldink, Jan H., van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., de Knijff, Peter, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Wang, Jun, Li, Ning, Cao, Sujie, Bovenberg, Jasper A., van Ommen, Gert-Jan B., and Arakelyan, Arsen

Published
2019

38. Mendelian randomization of blood lipids for coronary heart disease

Author

Redline, Susan, Sofat, Reecha, Shah, Sonia, Sivapalaratnam, Suthesh, Swerdlow, Daniel I., White, Jon, North, Kari E., Patel, Sanjay R., Engmann, Jorgen, Holmes, Michael V., Fornage, Myriam, Elbers, Clara C., Almoguera, Berta, Lanktree, Matthew B., Padmanabhan, Sandosh, Shah, Tina, Cushman, Mary, Dale, Caroline E., Asselbergs, Folkert W., McLachlan, Stela, Palmer, Tom M., Nelson, Christopher P., Doevendans, Pieter A., Hoogeveen, Ron C., Giambartolomei, Claudia, Zabaneh, Delilah, Tragante, Vinicius, van Iperen, Erik P.A., Drenos, Fotios, Finan, Chris, Balmforth, Anthony J., and Hall, Alistair S.

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

AimsTo investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization.Methods and resultsWe developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10−6); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75).ConclusionThe genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.

Published
2015
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39. Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations

Author

Beitelshees, Amber, Padmanabhan, Sandosh, Peters, Annette, Barnes, Michael R., O'Connell, Jeffrey R., Karczewski, Konrad J, Monda, Keri L., Bauer, Florianne, Lamonte, Michael J., Guo, Yiran, Peter, Inga, Shaffer, Jonathan, Boer, Jolanda M.A., Gong, Yan, Elbers, Clara C., Gieger, Christian, Burke, Gregory, Lanktree, Matthew B., Cooper-Dehoff, Rhonda M., Heard-Costa, Nancy, Mcdonough, Caitrin, Gorski, Mathias, Onland-Moret, N. Charlotte, Berenson, Gerald S., Chen, Wei, Yoneyama, Sachiko, Cade, Brian, Baumert, Jens, Ordovas, Jose, Johnson, Toby, Nelson, Christopher P., and Gaunt, Tom R.

Abstract

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20–80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10−6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β ± SE, 0.048 ± 0.008, P = 7.7 × 10−9) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10−7) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10−6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10−6) and rs1037575-A in ATBDB4 (β = 0.046 ± 0.01, P = 2.2 × 10−6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

Published
2014
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40. Mendelian randomization of blood lipids for coronary heart disease

Author

Holmes, Michael V., Asselbergs, Folkert W., Palmer, Tom M., Drenos, Fotios, Lanktree, Matthew B., Nelson, Christopher P., Dale, Caroline E., Padmanabhan, Sandosh, Finan, Chris, Swerdlow, Daniel I., Tragante, Vinicius, van Iperen, Erik P.A., Sivapalaratnam, Suthesh, Shah, Sonia, Elbers, Clara C., Shah, Tina, Engmann, Jorgen, Giambartolomei, Claudia, White, Jon, Zabaneh, Delilah, Sofat, Reecha, McLachlan, Stela, Doevendans, Pieter A., Balmforth, Anthony J., Hall, Alistair S., North, Kari E., Almoguera, Berta, Hoogeveen, Ron C., Cushman, Mary, Fornage, Myriam, Patel, Sanjay R., Redline, Susan, Siscovick, David S., Tsai, Michael Y., Karczewski, Konrad J., Hofker, Marten H., Verschuren, W. Monique, Bots, Michiel L., van der Schouw, Yvonne T., Melander, Olle, Dominiczak, Anna F., Morris, Richard, Ben-Shlomo, Yoav, Price, Jackie, Kumari, Meena, Baumert, Jens, Peters, Annette, Thorand, Barbara, Koenig, Wolfgang, Gaunt, Tom R., Humphries, Steve E., Clarke, Robert, Watkins, Hugh, Farrall, Martin, Wilson, James G., Rich, Stephen S., de Bakker, Paul I.W., Lange, Leslie A., Davey Smith, George, Reiner, Alex P., Talmud, Philippa J., Kivimäki, Mika, Lawlor, Debbie A., Dudbridge, Frank, Samani, Nilesh J., Keating, Brendan J., Hingorani, Aroon D., and Casas, Juan P.

Subjects
Male, Cardiac & Cardiovascular Systems, Genotype, Genotyping Techniques, Epidemiology, Coronary Artery Disease, Heart disease, 1102 Cardiovascular Medicine And Haematology, Polymorphism, Single Nucleotide, Risk Assessment, Gene Frequency, Clinical Research, GENETIC-VARIANTS, INSTRUMENTAL VARIABLES, Mendelian randomization, Humans, Cardiac and Cardiovascular Systems, CHOLESTEROL LEVELS, Aetiology, CARDIOVASCULAR EVENTS, METAANALYSIS, Triglycerides, Science & Technology, Cholesterol, HDL, VASCULAR-DISEASE, UCLEB consortium, Mendelian Randomization Analysis, Middle Aged, Heart Disease, Lipids, Mendelian Randomization, TRIALS, ATHEROSCLEROSIS, Cardiovascular System & Hematology, Case-Control Studies, Cardiovascular System & Cardiology, RISK-FACTORS, Female, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, HIGH-DENSITY-LIPOPROTEIN
Abstract

Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10−6); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain. M.V.H. was funded by a UK Medical Research Council Population Health Scientist Fellowship (G0802432). F.W.A. is supported by UCL Hospitals NIHR Biomedical Research Centre. D.I.S. is supported by a Medical Research Council Doctoral Training Award and a grant from the Rosetrees Foundation. ME.K. is supported by the National Institute of Aging and the National Heart, Lung and Blood Institute (HL36310). S.E.H. and P.J.T. are supported by the British Heart Foundation (BHF RG 08/008, PG/07/133/24260), UK Medical Research Council, the US National Institutes of Health (grant NHLBI 33014) and Du Pont Pharma, Wilmington, USA. N.J.S. holds a Chair funded by the British Heart Foundation and is an NIHR Senior Investigator. MI.K. is supported by the National Institute of Aging, the Medical Research Council, the British Heart Foundation, and the National Heart, Lung and Blood Institute and the Academy of Finland. A.D.H. and J.P.C. are supported by the National Institute of Health Research University College London Hospitals Biomedical Research Centre. Funding to pay the Open Access publication charges for this article was provided by RCUK.

Published
2014

41. Causal Effects of Body Mass Index on Cardiometabolic Traits and Events: A Mendelian Randomization Analysis

Author

Siscovick, David S., Buxbaum, Sarah, Tsai, Michael Y., Elbers, Clara C., Lanktree, Matthew B., Patel, Sanjay R., Fornage, Myriam, Redline, Susan, Price, Tom S., de Bakker, Paul I.W., Almoguera, Berta, van der Schouw, Yvonne T., Cushman, Mary, Palmer, Tom, Li, Jin, Schadt, Eric E., Curtis, Sean P., Asselbergs, Folkert W., Rich, Stephen S., Casas, Juan P., Hoogeveen, Ron C., Lange, Leslie A., Guo, Yiran, Chandrupatla, Hareesh R., Li, Yun R., Holmes, Michael V., Hingorani, Aroon D., North, Kari E., Wilson, James G., Swerdlow, Daniel I., FitzGerald, Garret A., and Hakonarson, Hakon

Abstract

(The American Journal of Human Genetics 94, 198–208; February 6, 2014)

Published
2014
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42. Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci

Author

Nelson, Christopher P., Kleber, Marcus E., Guo, Wei, Gieger, Christian, Ganesh, Santhi K., McDonough, Caitrin W., Pankratz, Nathan, Lanktree, Matthew B., Farrall, Martin, Gaunt, Tom R., Fischer, Mary E., Barnes, Michael R., Karczewski, Konrad J., Barnard, John, Chang, Yen-Pei Christy, Smith, Erin N., Meijs, Matthijs F.L., Melander, Olle, Gong, Yan, Almoguera, Berta, Leach, Irene Mateo, Gho, Johannes M.I.H., Baumert, Jens, Isaacs, Aaron, Franceschini, Nora, Holmes, Michael V., Padmanabhan, Sandosh, Johnson, Toby, Nolte, Ilja M., Tragante, Vinicius, Goel, Anuj, and Elbers, Clara C.

Abstract

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10−7) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

Published
2014
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43. Gene-centric meta-analyses for central adiposity traits in up to 57,412 individuals of European descent confirm known loci and reveal several novel associations

Author

Yoneyama, Sachiko, Guo, Yiran, Lanktree, Matthew B., Barnes, Michael R., Elbers, Clara C., Karczewski, Konrad J., Padmanabhan, Sandosh, Bauer, Florianne, Baumert, Jens, Beitelshees, Amber, Berenson, Gerald S., Boer, Jolanda M.A., Burke, Gregory, Cade, Brian, Chen, Wei, Cooper-DeHoff, Rhonda M., Gaunt, Tom R., Gieger, Christian, Gong, Yan, Gorski, Mathias, Heard-Costa, Nancy, Johnson, Toby, Lamonte, Michael J., Mcdonough, Caitrin, Monda, Keri L., Onland-Moret, N. Charlotte, Nelson, Christopher P., O’Connell, Jeffrey R., Ordovas, Jose, Peter, Inga, Peters, Annette, Shaffer, Jonathan, Shen, Haiqinq, Smith, Erin, Speilotes, Liz, Thomas, Fridtjof, Thorand, Barbara, Verschuren, W. M. Monique, Anand, Sonia S., Dominiczak, Anna, Davidson, Karina W., Hegele, Robert A., Heid, Iris, Hofker, Marten H., Huggins, Gordon S., Illig, Thomas, Johnson, Julie A., Kirkland, Susan, Konig, Wolfgang, Langaee, Taimour Y., Mccaffery, Jeanne, Melander, Olle, Mitchell, Braxton D., Munroe, Patricia, Murray, Sarah S., Papanicolaou, George, Redline, Susan, Reilly, Muredach, Samani, Nilesh J., Schork, Nicholas J., Van Der Schouw, Yvonne T., Shimbo, Daichi, Shuldiner, Alan R., Tobin, Martin D., Wijmenga, Cisca, Yusuf, Salim, Hakonarson, Hakon, Lange, Leslie A., Demerath, Ellen W., Fox, Caroline S., North, Kari E., Reiner, Alex P., Keating, Brendan, Taylor, Kira C., Look AHEAD Research Group, GIANT Consortium, and CARe IBC Consortium

Subjects
Meta-analysis, FOS: Biological sciences, Genetics, Medicine, Obesity--Genetic aspects, Adipose tissues--Analysis, Medical sciences
Abstract

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes, and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57,412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20 to 80. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50,000 cosmopolitan tagged SNPs across ∼2,100 cardiovascular-related genes. Each trait was modeled as a function of age, study site, and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P

Published
2013
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44. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, and Bovenberg, Jasper A.

Published
2015

45. Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration

Author

Lanktree, Matthew B, Elbers, Clara C, Li, Yun, Zhang, Guosheng, Duan, Qing, Karczewski, Konrad J, Guo, Yiran, Tragante, Vinicius, North, Kari E, Cushman, Mary, Asselbergs, Folkert W, Wilson, James G, Lange, Leslie A, Drenos, Fotios, Reiner, Alex P, Barnes, Michael R, Keating, Brendan J, Lanktree, Matthew B, Elbers, Clara C, Li, Yun, Zhang, Guosheng, Duan, Qing, Karczewski, Konrad J, Guo, Yiran, Tragante, Vinicius, North, Kari E, Cushman, Mary, Asselbergs, Folkert W, Wilson, James G, Lange, Leslie A, Drenos, Fotios, Reiner, Alex P, Barnes, Michael R, and Keating, Brendan J

Published
2015

46. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., de Bakker, Paul I W, CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., and de Bakker, Paul I W

Published
2015

47. Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1 is associated with HDL concentration

Author

Experimentele Afd. Cardiologie 1, Circulatory Health, Cardiologie, Lanktree, Matthew B, Elbers, Clara C, Li, Yun, Zhang, Guosheng, Duan, Qing, Karczewski, Konrad J, Guo, Yiran, Tragante, Vinicius, North, Kari E, Cushman, Mary, Asselbergs, Folkert W, Wilson, James G, Lange, Leslie A, Drenos, Fotios, Reiner, Alex P, Barnes, Michael R, Keating, Brendan J, Experimentele Afd. Cardiologie 1, Circulatory Health, Cardiologie, Lanktree, Matthew B, Elbers, Clara C, Li, Yun, Zhang, Guosheng, Duan, Qing, Karczewski, Konrad J, Guo, Yiran, Tragante, Vinicius, North, Kari E, Cushman, Mary, Asselbergs, Folkert W, Wilson, James G, Lange, Leslie A, Drenos, Fotios, Reiner, Alex P, Barnes, Michael R, and Keating, Brendan J

Published
2015

48. Mendelian randomization of blood lipids for coronary heart disease

Author

Cardiologie, Circulatory Health, Public Health Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, CMM Groep Kaaij, JC onderzoeksprogramma Methodologie, Cancer, Holmes, Michael V., Asselbergs, Folkert W., Palmer, Tom M., Drenos, Fotios, Lanktree, Matthew B., Nelson, Christopher P., Dale, Caroline E., Padmanabhan, Sandosh, Finan, Chris, Swerdlow, Daniel I., Tragante, Vinicius, Van Iperen, Erik P A, Sivapalaratnam, Suthesh, Shah, Sonia, Elbers, Clara C., Shah, Tina, Engmann, Jorgen, Giambartolomei, Claudia, White, Jon, Zabaneh, Delilah, Sofat, Reecha, McLachlan, Stela, Doevendans, Pieter A., Balmforth, Anthony J., Hall, Alistair S., North, Kari E., Almoguera, Berta, Hoogeveen, Ron C., Cushman, Mary, Fornage, Myriam, Patel, Sanjay R., Redline, Susan, Siscovick, David S., Tsai, Michael Y., Karczewski, Konrad J., Hofker, Marten H., Verschuren, W. Monique, Bots, Michiel L., Van Der Schouw, Yvonne T., Melander, Olle, Dominiczak, Anna F., Morris, Richard, Ben-Shlomo, Yoav, Price, Jackie, Kumari, Meena, Baumert, Jens, Peters, Annette, Thorand, Barbara, Koenig, Wolfgang, Gaunt, Tom R., Humphries, Steve E., Clarke, Robert, Watkins, Hugh, Farrall, Martin, Wilson, James G., Rich, Stephen S., De Bakker, Paul I W, Lange, Leslie A., Smith, George Davey, Reiner, Alex P., Talmud, Philippa J., Kivimäki, Mika, Lawlor, Debbie A., Dudbridge, Frank, Samani, Nilesh J., Keating, Brendan J., Hingorani, Aroon D., Casas, Juan P., Cardiologie, Circulatory Health, Public Health Epidemiologie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 5, Cardiovasculaire Epidemiologie, CMM Groep Kaaij, JC onderzoeksprogramma Methodologie, Cancer, Holmes, Michael V., Asselbergs, Folkert W., Palmer, Tom M., Drenos, Fotios, Lanktree, Matthew B., Nelson, Christopher P., Dale, Caroline E., Padmanabhan, Sandosh, Finan, Chris, Swerdlow, Daniel I., Tragante, Vinicius, Van Iperen, Erik P A, Sivapalaratnam, Suthesh, Shah, Sonia, Elbers, Clara C., Shah, Tina, Engmann, Jorgen, Giambartolomei, Claudia, White, Jon, Zabaneh, Delilah, Sofat, Reecha, McLachlan, Stela, Doevendans, Pieter A., Balmforth, Anthony J., Hall, Alistair S., North, Kari E., Almoguera, Berta, Hoogeveen, Ron C., Cushman, Mary, Fornage, Myriam, Patel, Sanjay R., Redline, Susan, Siscovick, David S., Tsai, Michael Y., Karczewski, Konrad J., Hofker, Marten H., Verschuren, W. Monique, Bots, Michiel L., Van Der Schouw, Yvonne T., Melander, Olle, Dominiczak, Anna F., Morris, Richard, Ben-Shlomo, Yoav, Price, Jackie, Kumari, Meena, Baumert, Jens, Peters, Annette, Thorand, Barbara, Koenig, Wolfgang, Gaunt, Tom R., Humphries, Steve E., Clarke, Robert, Watkins, Hugh, Farrall, Martin, Wilson, James G., Rich, Stephen S., De Bakker, Paul I W, Lange, Leslie A., Smith, George Davey, Reiner, Alex P., Talmud, Philippa J., Kivimäki, Mika, Lawlor, Debbie A., Dudbridge, Frank, Samani, Nilesh J., Keating, Brendan J., Hingorani, Aroon D., and Casas, Juan P.

Published
2015

49. The Genome of the Netherlands:design, and project goals

Author

Boomsma, Dorret I., Wijmenga, Cisca, Slagboom, Eline P., Swertz, Morris A., Karssen, Lennart C., Abdellaoui, Abdel, Ye, Kai, Guryev, Victor, Vermaat, Martijn, van Dijk, Freerk, Francioli, Laurent C., Hottenga, Jouke Jan, Laros, Jeroen F. J., Li, Qibin, Li, Yingrui, Cao, Hongzhi, Chen, Ruoyan, Du, Yuanping, Li, Ning, Cao, Sujie, van Setten, Jessica, Menelaou, Androniki, Pulit, Sara L., Hehir-Kwa, Jayne Y., Beekman, Marian, Elbers, Clara C., Byelas, Heorhiy, de Craen, Anton J. M., Deelen, Patrick, Dijkstra, Martijn, den Dunnen, Johan T., de Knijff, Peter, Houwing-Duistermaat, Jeanine, Koval, Vyacheslav, Estrada, Karol, Hofman, Albert, Kanterakis, Alexandros, van Enckevort, David, Mai, Hailiang, Kattenberg, Mathijs, van Leeuwen, Elisabeth M., Neerincx, Pieter B. T., Oostra, Ben, Rivadeneira, Fernanodo, Suchiman, Eka H. D., Uitterlinden, Andre G., Willemsen, Gonneke, Wolffenbuttel, Bruce H., Wang, Jun, de Bakker, Paul I. W., van Ommen, Gert-Jan, van Duijn, Cornelia M., Boomsma, Dorret I., Wijmenga, Cisca, Slagboom, Eline P., Swertz, Morris A., Karssen, Lennart C., Abdellaoui, Abdel, Ye, Kai, Guryev, Victor, Vermaat, Martijn, van Dijk, Freerk, Francioli, Laurent C., Hottenga, Jouke Jan, Laros, Jeroen F. J., Li, Qibin, Li, Yingrui, Cao, Hongzhi, Chen, Ruoyan, Du, Yuanping, Li, Ning, Cao, Sujie, van Setten, Jessica, Menelaou, Androniki, Pulit, Sara L., Hehir-Kwa, Jayne Y., Beekman, Marian, Elbers, Clara C., Byelas, Heorhiy, de Craen, Anton J. M., Deelen, Patrick, Dijkstra, Martijn, den Dunnen, Johan T., de Knijff, Peter, Houwing-Duistermaat, Jeanine, Koval, Vyacheslav, Estrada, Karol, Hofman, Albert, Kanterakis, Alexandros, van Enckevort, David, Mai, Hailiang, Kattenberg, Mathijs, van Leeuwen, Elisabeth M., Neerincx, Pieter B. T., Oostra, Ben, Rivadeneira, Fernanodo, Suchiman, Eka H. D., Uitterlinden, Andre G., Willemsen, Gonneke, Wolffenbuttel, Bruce H., Wang, Jun, de Bakker, Paul I. W., van Ommen, Gert-Jan, and van Duijn, Cornelia M.

Published
2014

50. Causal effects of body mass index on cardiometabolic traits and events:a Mendelian randomization analysis

Author

Holmes, Michael V., Lange, Leslie A., Palmer, Tom, Lanktree, Matthew B., North, Kari E., Almoguera, Berta, Buxbaum, Sarah, Chandrupatla, Hareesh R., Elbers, Clara C., Guo, Yiran, Hoogeveen, Ron C., Li, Jin, Li, Yun R., Swerdlow, Daniel I., Cushman, Mary, Price, Tom S., Curtis, Sean P., Fornage, Myriam, Hakonarson, Hakon, Patel, Sanjay R., Redline, Susan, Siscovick, David S., Tsai, Michael Y., Wilson, James G., van der Schouw, Yvonne T., FitzGerald, Garret A., Hingorani, Aroon D., Casas, Juan P., de Bakker, Paul I. W., Rich, Stephen S., Schadt, Eric E., Asselbergs, Folkert W., Reiner, Alex P., Keating, Brendan J., Holmes, Michael V., Lange, Leslie A., Palmer, Tom, Lanktree, Matthew B., North, Kari E., Almoguera, Berta, Buxbaum, Sarah, Chandrupatla, Hareesh R., Elbers, Clara C., Guo, Yiran, Hoogeveen, Ron C., Li, Jin, Li, Yun R., Swerdlow, Daniel I., Cushman, Mary, Price, Tom S., Curtis, Sean P., Fornage, Myriam, Hakonarson, Hakon, Patel, Sanjay R., Redline, Susan, Siscovick, David S., Tsai, Michael Y., Wilson, James G., van der Schouw, Yvonne T., FitzGerald, Garret A., Hingorani, Aroon D., Casas, Juan P., de Bakker, Paul I. W., Rich, Stephen S., Schadt, Eric E., Asselbergs, Folkert W., Reiner, Alex P., and Keating, Brendan J.

Abstract

Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses by using a genetic score (GS) comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate the causal role of BMI in cardiometabolic traits and events. We used eight population-based cohorts, including 34,538 European-descent individuals (4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke cases). A 1 kg/m(2) genetically elevated BMI increased fasting glucose (0.18 mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure (0.70 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1 kg/m(2) genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95% CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of 1.04 (95% CI = 0.97-1.12) per 1 kg/m(2) increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits; however, whether BMI causally impacts CHD risk requires further evidence.

Published
2014

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